The overall objective of this research is to study factors which control pulmonary circulation during the transition from fetus to neonate. Specifically, we will explore the interrelationship of physical (gaseous ventilation per se) and chemical (PO2, PCO2) changes and the release of vasoactive substances when the fetal lung is ventilated with air. We have shown that the decrease in pulmonary vascular resistance upon ventilation of a fetal goat lung with air has a rapid and a slower component. We will determine the relationships of 1) gaseous ventilation per se and 2) changes in blood gases and pH to each of these components. In addition, we will measure release of arachidonic acid metabolite substances, some of which we believe could be possible mediators of pulmonary vasodilation. Pulmonary arterial and venous levels of prostaglandins are measured in unventilated fetuses and following ventilation by chromatographic purification and isolation and electron capture detection of appropriate derivatives. Physiological parameters are simultaneously monitored. Fetuses are ventilated with gas mixtures that do not change fetal blood gases and those that do. We will attempt to gather data implying cause-effect relationships between vasoactive substances released and pulmonary vascular resistance changes by utilizing synthesis inhibitors. Abnormal transition from fetal to neonatal circulatory patterns is seen in persistent fetal circulation, persistent pulmonary hypertension, and progressive pulmonary hypertension. Understanding of the mechanisms behind the transition from fetal to neonatal circulatory patterns is vital to the treatment of newborns with abnormal transitions.